184 Form

1

Medical Policy Axillary Reverse Mapping for Prevention of Breast Cancer-Related Lymphedema Table of Contents • Policy: Commercial • Coding Information
• Information Pertaining to All Policies
• Policy: Medicare • Description
• References
• Authorization Information • Policy History

Policy Number: 184 BCBSA Reference Number: 7.01.173 (For Plan internal use only) NCD/LCD: N/A Related Policies
None Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity
Medicare HMO BlueSM and Medicare PPO BlueSM Members

Axillary reverse mapping/reverse lymphatic mapping performed during sentinel lymph node biopsy to prevent lymphedema in individuals who are being treated for breast cancer is considered INVESTIGATIONAL.

Axillary reverse mapping/reverse lymphatic mapping performed during axillary lymph node dissection to prevent lymphedema in individuals who are being treated for breast cancer is considered INVESTIGATIONAL.

Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient Commercial Managed Care (HMO and POS) This is not a covered service. Commercial PPO and Indemnity This is not a covered service. Medicare HMO BlueSM This is not a covered service. Medicare PPO BlueSM This is not a covered service.

2

CPT Codes / HCPCS Codes / ICD Codes
Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable. CPT Codes There are not any specific codes for this procedure. Description Lymphedema Lymphedema is an accumulation of fluid due to a disruption of lymphatic drainage. Lymphedema can be caused by congenital or inherited abnormalities in the lymphatic system (primary lymphedema) but is most often caused by acquired damage to the lymphatic system (secondary lymphedema). Breast cancer treatment is one of the most common causes of secondary lymphedema. Specific treatment-associated risk factors associated with lymphedema development include: • Lymphadenectomy • Dissection or disruption of axillary lymph nodes; increasing the number of dissected/disrupted lymph nodes increases lymphedema risk • Radiation therapy.

The risk of breast cancer-related lymphedema is also increased in overweight or obese individuals, and in those with postoperative infections. Studies have suggested that Black breast cancer survivors are nearly 2.2 times more likely to develop breast cancer-related lymphedema compared to White breast cancer survivors.1, These observations may be linked to racial disparities with regards to access to treatment and the types of treatments received. Black women are more likely than White women to undergo axillary lymph node dissection, which is associated with greater morbidity than the less invasive sentinel lymph node biopsy. While this may be explained in part by Black individuals having a higher likelihood of being diagnosed with more aggressive tumors, there is evidence that even when adjusting for stage and grade of tumors, Black women are more likely to undergo axillary lymph node dissection, putting Black women at greater risk of breast cancer-related lymphedema. Additionally, Black breast cancer survivors, on average, have higher body mass indexes than White breast cancer survivors, which could contribute to the development of lymphedema in this setting as well.

Development of lymphedema may take months or years following breast cancer treatment, and the true prevalence of breast cancer-related lymphedema is unclear.2, Systematic reviews have found lymphedema rates up to 13% in individuals undergoing sentinel lymph node biopsy (SNLB) and as high as 77% in those undergoing axillary lymph node dissection (ANLD).3, The addition of radiation therapy to SNLB or ANLD may also increase risk of lymphedema. A prospective study of 1,815 individuals published in 2020 found a 5-year cumulative incidence of breast cancer-related lymphedema of 9.5%, which ranged widely from 8% to 30% when stratified according to type of treatment. The lowest incidence of lymphedema was found among those undergoing SLNB only (8%), increasing to 11% for SNLB + regional lymph node radiation, 25% for ANLD only, and 30% for ANLD + RLNR.4, While SNLB was associated with a lower lymphedema risk, some risk remains, particularly for those with multiple positive axillary nodes for whom the standard for care is ANLD with or without radiation.

Early and ongoing treatment of lymphedema is necessary. Conservative therapy may consist of several features depending on the severity of the lymphedema. Patients are educated on the importance of self- care including hygiene practices to prevent infection, maintaining ideal body weight through diet and exercise, and limb elevation. Compression therapy consists of repeatedly applying padding and bandages or compression garments. Manual lymphatic drainage is a light pressure massage performed by trained physical therapists or patients designed to move fluid from obstructed areas into functioning

3

lymph vessels and lymph nodes. Complete decongestive therapy is a multiphase treatment program involving all of the previously mentioned conservative treatment components at different intensities. Pneumatic compression pumps may also be considered as an adjunct to conservative therapy or as an alternative to self-manual lymphatic drainage in patients who have difficulty performing self-manual lymphatic drainage. In patients with more advanced lymphedema after fat deposition and tissue fibrosis have occurred, palliative surgery using reductive techniques such as liposuction may be performed.

Axillary Reverse Mapping Axillary reverse mapping (ARM) involves subcutaneous administration of blue dye, fluorescence (i.e., indocyanine green), or radioisotopes to allow for visualization of the lymphatic drainage pathways of the arm and breast. This visualization is intended to distinguish and enable preservation of axillary lymph nodes and lymphatics in individuals undergoing SLNB and/or ANLD. It is believed that because the axilla and breast have mostly separate drainage pathways, the risk of lymphedema is reduced by avoiding the removal of lymph nodes and lymphatics that only drain the axilla identified through ARM. In the event that ARM reveals that the axillary nodes cannot be spared, for example due to crossover of sentinel and axillary nodes, lymphatic physiologic microsurgery has been explored as a method to preserve the axillary nodes, though evidence is limited.

Summary Description Surgery and radiotherapy for breast cancer can lead to lymphedema and are some of the most common causes of secondary lymphedema. Lymphedema is associated with a significant impact on quality of life, and there is no cure for lymphedema. Axillary reverse mapping, also called reverse lymphatic mapping, has been developed with the intent of sparing axillary lymph nodes and lymphatics during breast cancer surgery, minimizing disruption and potentially reducing the risk of subsequent lymphedema development.

Summary of Evidence For individuals with breast cancer undergoing sentinel lymph node biopsy (SLNB) who receive axillary reverse mapping (ARM), the evidence includes nonrandomized studies and systematic reviews of those studies. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Evidence from 2 systematic reviews found ARM identified axillary lymphatics in about 38% of individuals undergoing SLNB, with lymphedema rates of 2% to 3% in individuals who underwent ARM during SLNB. Other outcomes such as quality of life were not reported. The systematic reviews had numerous limitations, including unclear mean duration of follow-up and inclusion of only single-arm, uncontrolled studies. Evidence from well-designed RCTs or controlled cohort studies is needed to determine the net health benefit of ARM in SLNB. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with breast cancer undergoing axillary lymph node dissection (ALND) who receive ARM, the evidence includes randomized controlled trials (RCTs), nonrandomized studies, and systematic reviews of those studies. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Pooled evidence from a systematic review of 5 RCTs showed a lower risk of lymphedema with ARM compared with no ARM (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.13 to 0.29), and another systematic review of RCTs and nonrandomized studies found a pooled lymphedema prevalence of 14% and lower risk of lymphedema with ARM and preserved axillary lymph nodes compared with resected lymph nodes (OR, 0.27; 95% CI, 0.20 to 0.36). In the same review, ARM was associated with an 82% identification rate of axillary lymph nodes and lymphatics, and a crossover rate between ARM and sentinel lymph nodes of 12%. Other health outcomes, including quality of life, were not reported. The safety of ARM in ALND has not been established, and the rate of metastatic ARM nodes was 13% based on pooled analysis of 27 studies in 1 systematic review. ARM in ALND was associated with a lower risk of lymphedema in the largest RCT conducted to date, which was also included in the systematic reviews, but oncological safety could not be determined, and the trial also had important study relevance and design limitations. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Policy History

4

Date Action 1/2026 Annual policy review. References updated. Policy statements unchanged. 1/2025 Annual policy review. References updated. Policy statements unchanged. 1/2024 Annual policy review. References updated. Policy statements unchanged. 4/2023 New medical policy describing investigational indications. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines References

1. Dean LT, Kumar A, Kim T, et al. Race or Resource? BMI, Race, and Other Social Factors as Risk Factors for Interlimb Differences among Overweight Breast Cancer Survivors with Lymphedema. J Obes. 2016; 2016: 8241710. PMID 27433356
2. McLaughlin SA, Stout NL, Schaverien MV. Avoiding the Swell: Advances in Lymphedema Prevention, Detection, and Management. Am Soc Clin Oncol Educ Book. Mar 2020; 40: 1-10. PMID 32315238
3. Shao X, Sun B, Shen Y. Axillary reverse mapping (ARM): where to go. Breast Cancer. Jan 2019; 26(1): 1-10. PMID 29961238
4. Naoum GE, Roberts S, Brunelle CL, et al. Quantifying the Impact of Axillary Surgery and Nodal Irradiation on Breast Cancer-Related Lymphedema and Local Tumor Control: Long-Term Results From a Prospective Screening Trial. J Clin Oncol. Oct 10 2020; 38(29): 3430-3438. PMID 32730184
5. U.S. Food and Drug Administration. Isosulfan Blue Product Label. 2021. https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42f2d62a-c7f2-4706-87bc- 64f3e72d63a9. Accessed September 15, 2025.
6. U.S. Food and Drug Administration. Indocyanine Green for Injection Product Label. 2020. https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91c206e8-fab9-4bf3-afcf- 304eddf0d54e. Accessed September 15, 2025.
7. National Lymphedema Network. Risk Reduction Practices. https://lymphnet.org/page/risk-reduction/. Accessed September 15, 2025.
8. Cemal Y, Pusic A, Mehrara BJ. Preventative measures for lymphedema: separating fact from fiction. J Am Coll Surg. Oct 2011; 213(4): 543-51. PMID 21802319
9. Asdourian MS, Skolny MN, Brunelle C, et al. Precautions for breast cancer-related lymphoedema: risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis. Lancet Oncol. Sep 2016; 17(9): e392-405. PMID 27599144
10. Executive Committee of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2020 Consensus Document of the International Society of Lymphology. Lymphology. 2020; 53(1): 3-19. PMID 32521126
11. Pusic AL, Cemal Y, Albornoz C, et al. Quality of life among breast cancer patients with lymphedema: a systematic review of patient-reported outcome instruments and outcomes. J Cancer Surviv. Mar 2013; 7(1): 83-92. PMID 23212603
12. Coriddi M, Dayan J, Sobti N, et al. Systematic Review of Patient-Reported Outcomes following Surgical Treatment of Lymphedema. Cancers (Basel). Feb 29 2020; 12(3). PMID 32121343
13. Parks RM, Cheung KL. Axillary reverse mapping in N0 patients requiring sentinel lymph node biopsy - A systematic review of the literature and necessity of a randomised study. Breast. Jun 2017; 33: 57-
14. PMID 28282588
15. Wijaya WA, Peng J, He Y, et al. Clinical application of axillary reverse mapping in patients with breast cancer: A systematic review and meta-analysis. Breast. Oct 2020; 53: 189-200. PMID 32858404
16. Han C, Yang B, Zuo WS, et al. The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. PLoS One. 2016; 11(2): e0150285. PMID 26919589

5

16. Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy. Am J Surg. Oct 2009; 198(4): 482-7. PMID 19800452
17. Casabona F, Bogliolo S, Valenzano Menada M, et al. Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients. Ann Surg Oncol. Sep 2009; 16(9): 2459-63. PMID 19506954
18. Connor C, McGinness M, Mammen J, et al. Axillary reverse mapping: a prospective study in women with clinically node negative and node positive breast cancer. Ann Surg Oncol. Oct 2013; 20(10): 3303-7. PMID 23975287
19. Deng H, Chen L, Jia W, et al. Safety study of axillary reverse mapping in the surgical treatment for breast cancer patients. J Cancer Res Clin Oncol. Dec 2011; 137(12): 1869-74. PMID 21935615
20. Han JW, Seo YJ, Choi JE, et al. The efficacy of arm node preserving surgery using axillary reverse mapping for preventing lymphedema in patients with breast cancer. J Breast Cancer. Mar 2012; 15(1): 91-7. PMID 22493634
21. Kuusk U, Seyednejad N, McKevitt EC, et al. Axillary reverse mapping in breast cancer: a Canadian experience. J Surg Oncol. Dec 2014; 110(7): 791-5. PMID 25053441
22. Ma X, Wen S, Liu B, et al. Relationship between Upper Extremity Lymphatic Drainage and Sentinel Lymph Nodes in Patients with Breast Cancer. J Oncol. 2019; 2019: 8637895. PMID 31057616
23. Noguchi M, Yokoi M, Nakano Y. Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer. J Surg Oncol. Mar 01 2010; 101(3): 217-21. PMID 20063370
24. Ochoa D, Korourian S, Boneti C, et al. Axillary reverse mapping: five-year experience. Surgery. Nov 2014; 156(5): 1261-8. PMID 25444319
25. Rubio IT, Cebrecos I, Peg V, et al. Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer. J Surg Oncol. Jul 01 2012; 106(1): 89-93. PMID 22258666
26. Sakurai T, Endo M, Shimizu K, et al. Axillary reverse mapping using fluorescence imaging is useful for identifying the risk group of postoperative lymphedema in breast cancer patients undergoing sentinel node biopsies. J Surg Oncol. May 2014; 109(6): 612-5. PMID 24310418
27. Tummel E, Ochoa D, Korourian S, et al. Does Axillary Reverse Mapping Prevent Lymphedema After Lymphadenectomy?. Ann Surg. May 2017; 265(5): 987-992. PMID 27163955
28. Guo X, Jiao D, Zhu J, et al. The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials. Gland Surg. Apr 2021; 10(4): 1447-1459. PMID 33968696
29. Yuan Q, Wu G, Xiao SY, et al. Identification and Preservation of Arm Lymphatic System in Axillary Dissection for Breast Cancer to Reduce Arm Lymphedema Events: A Randomized Clinical Trial. Ann Surg Oncol. Oct 2019; 26(11): 3446-3454. PMID 31240591
30. Chang DW, Dayan J, Greene AK, et al. Surgical Treatment of Lymphedema: A Systematic Review and Meta-Analysis of Controlled Trials. Results of a Consensus Conference. Plast Reconstr Surg. Apr 01 2021; 147(4): 975-993. PMID 33761519
31. American Society of Breast Surgeons. Consensus Guideline on Axillary Management for Patients with In-Situ and Invasive Breast Cancer: A Concise Overview. 2022. Accessed September 15, 2025.
32. McLaughlin SA, DeSnyder SM, Klimberg S, et al. Considerations for Clinicians in the Diagnosis, Prevention, and Treatment of Breast Cancer-Related Lymphedema, Recommendations from an Expert Panel: Part 2: Preventive and Therapeutic Options. Ann Surg Oncol. Oct 2017; 24(10): 2827-
33. PMID 28766218